Alzheimer's disease (AD), the most common geriatric dementia, has become a major threat to aging baby boomers and presents one of the leading, long-term economic and health burdens to our society. The estimated cost of AD in the US for health care and hospice in the long run is projected to exceed $183 billion in 2011 and to reach over $1.1 trillion by 2050. The cumulative costs of care will break $20 trillion over the next 40 years. The major challenge AD presents today is that the disease cannot be diagnosed clinically, with confidence, until a majority of neurons have already degenerated in several key brain regions--including the hippocampus which is critical to memory functions. Thus, there is an urgent need to develop biomarkers that can detect AD at its earliest stages. Several promising biomarkers have been revealed to assist AD diagnosis at symptomatic stages as well as in an early phase of AD, mild cognitive impairment; however, all of these markers are either neuroimaging-based, which is quite expensive and has limited accessibility, or cerebrospinal fluid (CSF)-based, which carries relative risk to the patients when the samples are obtained by lumbar puncture. Lumbar puncture is also technically difficult to perform in routine clinical practices. Motivated by our recent discovery that tau species (proteins intimately involved in AD pathogenesis but not detectable in blood) presents itself in human saliva, with changes unique to AD, in this application we propose to develop practical assays using easily accessible saliva for AD diagnosis and progression or assessment of existing and future therapeutics. Salivary biomarkers, if confirmed in this SBIR Phase I application, can also be potentially used as a screening assay in the general population in a Phase II SBIR. The current investigations will be focused on tau and A species (another key component of AD pathology) with the goal of developing robust biomarkers that can be adapted swiftly to daily clinical practice, even in remote areas of developed countries or in developing countries. PUBLIC HEALTH RELEVANCE: Developing a user-friendly diagnostic tool using an easily accessible body fluid like saliva will greatly enhance the chance of diagnosing Alzheimer's disease in its early stages, thereby expanding the therapeutic window.